Serum <scp>anti‐GM2</scp> and <scp>anti‐GalNAc‐GD1a</scp> ganglioside <scp>IgG</scp> antibodies are biomarkers for immune‐mediated polyneuropathies in cats

Halstead, Susan K.; Jackson, Mark R.; Bianchi, Ezio; Rupp, Stefan; Granger, Nicolas; Menchetti, Marika; Galli, G; Freeman, Paul; Kaczmarska, Adriana; Bhatti, Sofie; Brocal, Josep; José-López, Roberto; Tipold, Andrea; Quintana, R. Gutierrez; Ives, Edward; Liatis, Theophanes; Neßler, Jasmin; Rusbridge, Clare; Willison, Hugh J.; Rupp, Angie

doi:10.1111/jns.12529

Cited by 1 publication

(1 citation statement)

References 38 publications

(103 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IgM anti-GM2 antibodies have been described throughout the spectrum of immune-mediated neuropathies, including Guillain-Barré syndrome (GBS) and its acute motor axonal variants, chronic inflammatory demyelinating polyneuropathy, and sensory demyelinating neuropathy with ataxia [ 20 , 21 , 32 , 34 – 38 ]. IgG anti-GM2 antibodies are a biomarker for immune-mediated polyneuropathies in cats [ 39 ]. Interestingly, the presence of IgM anti-GM2 antibodies is associated with preceding cytomegalovirus (CMV) infection in patients with GBS [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

IgM anti-GM2 antibodies in patients with multifocal motor neuropathy target Schwann cells and are associated with early onset

Budding,

Bos,

Dijkxhoorn

et al. 2024

J Neuroinflammation

View full text Add to dashboard Cite

Background Multifocal motor neuropathy (MMN) is a rare, chronic immune-mediated polyneuropathy characterized by asymmetric distal limb weakness. An important feature of MMN is the presence of IgM antibodies against gangliosides, in particular GM1 and less often GM2. Antibodies against GM1 bind to motor neurons (MNs) and cause damage through complement activation. The involvement of Schwann cells (SCs), expressing GM1 and GM2, in the pathogenesis of MMN is unknown. Methods Combining the data of our 2007 and 2015 combined cross-sectional and follow-up studies in Dutch patients with MMN, we evaluated the presence of IgM antibodies against GM1 and GM2 in serum from 124 patients with MMN and investigated their binding to SCs and complement-activating properties. We also assessed the relation of IgM binding and complement deposition with clinical characteristics. Results Thirteen out of 124 patients (10%) had a positive ELISA titer for IgM anti-GM2. Age at onset of symptoms was significantly lower in MMN patients with anti-GM2 IgM. IgM binding to SCs correlated with IgM anti-GM2 titers. We found no correlation between IgM anti-GM2 titers and MN binding or with IgM anti-GM1 titers. IgM binding to SCs decreased upon pre-incubation of serum with soluble GM2, but not with soluble GM1. IgM anti-GM2 binding to SCs correlated with complement activation, as reflected by increased C3 fixation on SCs and C5a formation in the supernatant. Conclusion Circulating IgM anti-GM2 antibodies define a subgroup of patients with MMN that has an earlier onset of disease. These antibodies probably target SCs specifically and activate complement, similarly as IgM anti-GM1 on MNs. Our data indicate that complement activation by IgM antibodies bound to SCs and MNs underlies MMN pathology.

show abstract